FK506 (tacrolimus) and its immunoreactive metabolites in whole blood of liver transplant patients and subjects with mild hepatic dysfunction.

Abstract

To determine the concentrations of FK506 and its metabolites in blood from liver transplant patients and subjects with hepatic dysfunction. HPLC was combined with an enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of FK506 and its immunoreactive metabolites in human whole blood. In four liver transplant patient, most of the immunoreactivity was seen in the HPLC fractions where unchanged FK506 eluted. FK506 accounted for about 95% or more of the total immunoreactivity in the first days of posttransplant. Immunoreactivity observed in the nonFK506 fractions ranged from 1.6% to 10.7% of the total immunoreactivity; about 30% of the nonFK506 immunoreactivity was due to M-III(15-O-demethyl FK506). Blood from subjects with mild hepatic dysfunction was examined at 1.5 and 6 hours after an oral and intravenous dose, respectively, by HPLC-ELISA. Regardless of the route of administration, more than 96% of the total immunoreactivity was recovered in the FK506 fraction. M-III was detected in the blood of 3 of 6 subjects after an oral dose, but in none of these after an intravenous dose. ELISA is an appropriate method for therapeutic drug monitoring of FK506.